Multilevel HierCC typing scheme for global genomic epidemiology and antimicrobial resistance surveillance of Campylobacter jejuni

Campylobacter jejuni is the most common bacterial cause of human gastroenteritis around the world. The disease burden and financial cost associated with C. jejuni pose significant challenges to the global public health system. A stable, scalable and standardised typing scheme is essential for epidemiological and AMR surveillance for prevention and control of C. jejuni infections. We curated and assembled a C. jejuni global whole genome sequencing (WGS) dataset of 63,012 publicly available Illumina short-read genomes. A C. jejuni global cgMLST scheme with 1161 core loci was developed using a representative subset of 2,587 genomes. HierCC clustering of the cgMLST profiles was performed for all levels and suitable HierCC levels were selected to enable epidemiological analysis. Antimicrobial resistance (AMR) prediction was performed using AbritAMR. A HierCC cluster was classified as a resistant cluster if [≥]80% of the isolates were resistant to at least one antibiotic.We selected 9 HierCC levels (HC2, HC4, HC6, HC12, HC19, HC55, HC100, HC167 and HC264) to form the multilevel HierCC scheme. The multilevel design allowed natural and genetically discrete clusters to be described consistently at both global and local scale. We showcased the utility of the scheme with identification of country and continent specific clusters at HC264 to HC19 levels and differentiation of animal host specific (specialist) from human infection (generalist) clusters at HC264 to HC55 levels. In the USA dataset from 2016 to 2022, a total of 276 resistant clusters were identified with 22 resistant clusters increasing in frequence in recent years. An increased prevalence of C. jejuni carrying 50S_L22 mutations in the USA was observed from 2016 to 2022, suggesting continuing selection pressure from macrolide use in the farm animals. We developed a novel multilevel HierCC typing scheme to standardise AMR surveillance and provide flexible typing resolution for both short- and long-term epidemiological investigations of C. jejuni at global and local levels.